Testing novel IL-27-based therapies for prostate cancer
Katrina Gee, Queen’s University
Lead Investigator Bio:
Dr Gee obtained her PhD in 2003 from the University of Ottawa, Department of Biochemistry, Microbiology and Immunology. She completed post-doctoral studies at the Ottawa Health Research Institute and the Children’s Hospital of Eastern Ontario Research Institute from 2003 to 2006. Her thesis and postdoctoral studies provided Dr Gee with a strong background in regulation of cytokine expression, function, and signalling pathways. Dr Gee joined the Department of Microbiology and Immunology (now the Department of Biomedical & Molecular Sciences) at Queen’s University as a tenure track Assistant Professor in 2007. Currently, the Gee lab has 4 graduate and 2 undergraduate students working on projects related to cancer and inflammation with a particular focus on the molecular biology of cytokines in human cancer and diseases. Dr Gee has published a career total of 40 peer reviewed scientific publications and has supervised over 25 graduate and undergraduate students in the last 10 years.
Cytokines are instant messengers of the immune system, alerting our body foreign substances. For diseases such as prostate cancer, cytokines represent potential therapeutics. In our study, we will investigate how a particular cytokine, called interleukin-27 (IL-27) can trigger killing of prostate cancer cells. Additionally, cytokines are critically important for orchestrating immune responses against cancer cells. Since cancer cells evolve to effectively hide from the body’s immune system, it is important to discover effective ways to make cancer cells more visible to our immune cells. We have shown that IL-27 promotes expression of receptors in prostate cancer cells that raises “red flags” that can alert immune cells to help destroy the prostate cancer cells. Therefore, the hypothesis of this project is two-fold: 1) IL-27 can directly enhance death of prostate cancer cells, and 2) IL-27 can enhance immune activity against prostate cancer cells. This work is significant because we will investigate the therapeutic potential of IL-27 alone and in combination with clinically relevant drugs.
IL-27 is a promising anti-cancer cytokine with therapeutic potential in prostate cancer. Similar to type I and II interferons (IFN), expression of IL-27 can reduce cancer cell viability and boost anti-cancer immunity. However, how to best leverage IL-27 for prostate cancer therapy requires further study in immune competent tumour models. We recently showed that IL-27 treated prostate cancer cells become sensitized to Toll-like receptor (TLR)-3-mediated cell death (Kourko et al, 2019, JICR, under review). In this application, we will extend these observations to murine prostate cancer cell lines that will allow testing in immune competent mice with prostate tumours. We will examine how IL-27 impacts TLR3-triggered prostate cancer cell death using a clinically relevant TLR3 ligand called poly-ICLC. We will also examine how IL-27 treatments may augment tumour immunogenicity and enhance activation of anti-tumour immune responses. These critical lines of investigation will serve to support further research into the potential use of IL-27 in combination with chemotherapeutic drugs. Leading to better therapies for aggressive forms of prostate cancer.
Impact on prostate cancer patients:
This project will the design of chemotherapetuic treatments with the goal of enhancing the function of the drugs and reducing the concentrations needed to effectively target cancer cells. This will also reduce harful side-effects of chemotherapy.